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Padalkar P, Yadadi SS, Vivekanandan G, Shetty SR, Andhare M, Pashine A, Vinay V, Desai V, Shetty RM. Salivary periostin levels as a non-invasive biomarker and their clinical correlates among healthy and periodontitis patients-a cross-sectional analytical study. FRONTIERS IN DENTAL MEDICINE 2025; 6:1512252. [PMID: 40177468 PMCID: PMC11961936 DOI: 10.3389/fdmed.2025.1512252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/19/2025] [Indexed: 04/05/2025] Open
Abstract
Background The diagnosis of periodontitis is primarily through clinical and radiographic assessments. However, it is difficult for clinicians to detect incipient periodontitis during the routine clinical assessment. Identifying people at risk for periodontitis and tracking disease development need a dependable biomarker. Currently, no biomarkers meet all the criteria required for an ideal diagnostic test. Therefore, the clinical utility of salivary periostin as a potential screening tool for periodontitis warrants further investigation, particularly through large samples across diverse populations. The present study aimed to investigate salivary periostin levels as a biomarker in individuals with periodontitis and healthy controls. Methods Forty-five patients with generalized periodontitis stage III grade A/B and an equivalent number of periodontally healthy controls were evaluated for plaque index (PI), gingival index (GI), pocket probing depth (PPD), and clinical attachment level (CAL). Unstimulated salivary samples from all subjects were taken, and periostin levels were quantified using an ELISA kit. Results The average salivary periostin levels were 4.63 in the healthy group and 1.24 in the periodontitis group (P < 0.05). The Spearman coefficient indicated a negative correlation between periostin levels and the gingival index (r = -0.761), plaque index (r = -0.780; P < 0.05), probing pocket depth (PPD) (r = -0.713; P < 0.05) and clinical attachment level (CAL) (r = -0.713; P < 0.05). Linear regression analysis validated the indirect correlation between salivary periostin levels and clinical indicators (Adjusted R square = 0.947). Conclusions Salivary periostin levels are associated with periodontal disease. Salivary periostin levels indirectly influence as a non-invasive biomarker of periodontitis. The biomarker periostin is effective for evaluating both healthy and diseased periodontium.
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Affiliation(s)
| | - Sunaina Shetty Yadadi
- Department of Preventive and Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Gopinath Vivekanandan
- Department of Periodontology, Vivekanandha Dental College for Women, Tiruchengodu, India
| | - Shishir Ram Shetty
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Mangesh Andhare
- Department of Periodontology, Aditya Dental College, Beed, India
| | - Aditi Pashine
- Associate Dentist, MyDentist, Hungerford, United Kingdom
| | - Vineet Vinay
- Department of Public Health Dentistry, Sinhgad Dental College and Hospital, Pune, India
| | - Vijay Desai
- Department of Clinical Sciences, College of Dentistry, Ajman University, Ajman, United Arab Emirates
- Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Raghavendra M. Shetty
- Department of Clinical Sciences, College of Dentistry, Ajman University, Ajman, United Arab Emirates
- Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
- Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research, Wardha, India
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Lou L, Peng K, Ouyang S, Ding W, Mo J, Yan J, Gong X, Liu G, Lu J, Yue P, Zhang K, Zhang J, Wang YD, Zhang XL. Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer. J Exp Clin Cancer Res 2025; 44:6. [PMID: 39762921 PMCID: PMC11706058 DOI: 10.1186/s13046-024-03266-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with the liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying the interaction between SCLC and liver microenvironment, fostering metastasis, remain unclear. METHODS SCLC patient tissue array, bioinformatics analysis were performed to demonstrate the role of periostin (POSTN) in SCLC progression, metastasis, and prognosis. Cell migration, invasion and sphere formation assay were performed to determine the oncogenic role of POSTN. RNA sequencing analysis was utilized to identify the key signaling pathway regulated by POSTN. Immunoprecipitation, immunofluorescence and co-culture system were used to clarify the mechanism of POSTN-NOTCH1 axis in tumor cells-hepatic stellate cells (HSCs) crosstalk. Subcutaneous xenograft model and liver metastasis model were established to examine the anti-tumor growth and metastases effect of targeting POSTN-NOTCH1 signaling axis. RESULTS Elevated expression of POSTN in SCLC is correlated with accelerated tumor progression and metastasis. Conditioned medium rich in POSTN derived from SCLC tumors demonstrates the ability to activate HSCs in the liver microenvironment. Mechanistically, POSTN emerges as a binding partner for the membrane receptor NOTCH1 and transducing the extracellular signals to intracellular fibroblasts. Furthermore, targeting the POSTN-NOTCH1 signaling axis proves effective in suppressing SCLC tumor growth and inhibiting liver metastasis. This study elucidates that the SCLC-derived secreted protein POSTN interacts with NOTCH1 on HSCs to promote the activation of HSCs, thereby providing a favorable microenvironment for liver metastasis. CONCLUSION These findings uncover the intricate communications between primary SCLC cells and HSCs in the tumor microenvironment mediated by the secreted protein POSTN in the context of liver metastasis. Consequently, targeting the POSTN-NOTCH1 signaling axis emerges as a promising therapeutic strategy for metastatic SCLC.
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Affiliation(s)
- Linlin Lou
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Keren Peng
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Shumin Ouyang
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Wen Ding
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China
| | - Jianshan Mo
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Jiayu Yan
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Xiaoxiao Gong
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Guopin Liu
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China
| | - Jinjian Lu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Peibin Yue
- Department of Medicine, Division of Hematology-Oncology, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Kai Zhang
- Department of Thoracic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Jian Zhang
- Department of Thoracic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
| | - Yan-Dong Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.
| | - Xiao-Lei Zhang
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
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De Oliveira Macena Y, Cezar MEN, Lira CBF, De Oliveira LBDM, Almeida TN, Costa ADAV, De Araujo BMD, de Almeida Junior D, Dantas HM, De Mélo EC, de Araújo ST, de França Júnior RR, Dos Santos Lemos Gurgel MA, de Carvalho Fraga CA. The roles of periostin derived from cancer-associated fibroblasts in tumor progression and treatment response. Cancer Metastasis Rev 2024; 44:11. [PMID: 39614015 DOI: 10.1007/s10555-024-10233-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 11/21/2024] [Indexed: 12/01/2024]
Abstract
Periostin (POSTN), a matricellular protein predominantly secreted by cancer-associated fibroblasts (CAFs), has emerged as a key regulator of cancer progression and therapy response. This review provides an overview of recent findings regarding the diverse roles of periostin in cancer therapy and its potential as a therapeutic target. Studies have elucidated periostin's involvement in tumorigenesis, including tumor growth, metastasis, chemotherapy resistance, and modulation of the tumor microenvironment (TME). CAFs periostin + play a central role in shaping the TME by remodeling the extracellular matrix (ECM) and promoting immune evasion, thus promoting tumor cell survival and dissemination. Elevated periostin expression has been correlated with poor prognosis across multiple cancer types, suggesting its utility as a prognostic biomarker. Periostin has been implicated in mediating resistance to chemotherapy, with CAFs periostin + establishing a pro-tumorigenic niche that confers protection to cancer cells against cytotoxic therapies. Targeting periostin or its downstream effectors presents a promising strategy to overcome therapy resistance and enhance treatment efficacy. While significant progress has been made in understanding the biological functions of periostin in cancer, gaps persist in elucidating its precise mechanisms of action and clinical relevance. Future research should focus on deciphering the signaling pathways and molecular interactions underlying periostin-mediated effects in the TME. Prospective clinical studies are warranted to evaluate periostin as a predictive biomarker and therapeutic target in cancer patients.
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Affiliation(s)
- Yasmin De Oliveira Macena
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Maria Eduarda Nunes Cezar
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Cinthya Brunelly Ferreira Lira
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | | | - Thais Noronha Almeida
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Ana Dora Alecio Virtuoso Costa
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Bernardo Mansur Dantas De Araujo
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Durval de Almeida Junior
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Henrique Macêdo Dantas
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Emanuel Cézar De Mélo
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Sandra Taveiros de Araújo
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Raimundo Rodrigues de França Júnior
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Maria Amélia Dos Santos Lemos Gurgel
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil
| | - Carlos Alberto de Carvalho Fraga
- Universidade Federal de Alagoas, Campus Arapiraca, Centro de Ciências Médicas, Av. Manoel Severino Barbosa, Bom Sucesso, Arapiraca, AL, CEP 57309-005, Brazil.
- CRID - Centro de Pesquisa em Doenças Inflamatórias, Av. Bandeirantes, R. Paineiras, 3900 - Casa 03 - Vila Monte Alegre, Ribeirão Preto, SP, 14049-900, Brazil.
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas (FCF), Universidade de São Paulo (USP), São Paulo, SP, Brazil.
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Yoshimura K, Ito Y, Suzuki M, Horie M, Nishiuchi T, Shintani-Domoto Y, Shigehara K, Oshima H, Oshima M, Goto A, Nojima T, Tsuzuki T, Mizokami A, Ikeda H, Maeda D. Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry. Pathol Int 2024; 74:187-196. [PMID: 38289139 DOI: 10.1111/pin.13409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/09/2024] [Accepted: 01/13/2024] [Indexed: 02/03/2024]
Abstract
Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82-year-old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid-Schiff staining-positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm-Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion.
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Affiliation(s)
- Kaori Yoshimura
- Department of Pathology, Kanazawa University Hospital, Kanazawa, Japan
| | - Yukinobu Ito
- Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Mina Suzuki
- Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Masafumi Horie
- Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Takumi Nishiuchi
- Division of Integrated Omics Research, Bioscience Core Facility, Research Canter for Experimental Modelling of Human Disease, Kanazawa University, Kanazawa, Japan
| | | | - Kazuyoshi Shigehara
- Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Hiroko Oshima
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Masanobu Oshima
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Akiteru Goto
- Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan
| | - Takayuki Nojima
- Department of Pathology, Kanazawa University Hospital, Kanazawa, Japan
| | - Toyonori Tsuzuki
- Department of Surgical Pathology, School of Medicine, Aichi Medical University, Nagoya, Japan
| | - Atsushi Mizokami
- Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Hiroko Ikeda
- Department of Pathology, Kanazawa University Hospital, Kanazawa, Japan
| | - Daichi Maeda
- Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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Attachaipanich T, Chattipakorn SC, Chattipakorn N. Current evidence regarding the cellular mechanisms associated with cancer progression due to cardiovascular diseases. J Transl Med 2024; 22:105. [PMID: 38279150 PMCID: PMC10811855 DOI: 10.1186/s12967-023-04803-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 12/13/2023] [Indexed: 01/28/2024] Open
Abstract
Several large cohort studies in cardiovascular disease (CVD) patients have shown an increased incidence of cancer. Previous studies in a myocardial infarction (MI) mouse model reported increased colon, breast, and lung cancer growth. The potential mechanisms could be due to secreted cardiokines and micro-RNAs from pathological hearts and immune cell reprogramming. A study in a MI-induced heart failure (HF) mouse demonstrated an increase in cardiac expression of SerpinA3, resulting in an enhanced proliferation of colon cancer cells. In MI-induced HF mice with lung cancer, the attenuation of tumor sensitivity to ferroptosis via the secretion of miR-22-3p from cardiomyocytes was demonstrated. In MI mice with breast cancer, immune cell reprogramming toward the immunosuppressive state was shown. However, a study in mice with renal cancer reported no impact of MI on tumor growth. In addition to MI, cardiac hypertrophy was shown to promote the growth of breast and lung cancer. The cardiokine potentially involved, periostin, was increased in the cardiac tissue and serum of a cardiac hypertrophy model, and was reported to increase breast cancer cell proliferation. Since the concept that CVD could influence the initiation and progression of several types of cancer is quite new and challenging regarding future therapeutic and preventive strategies, further studies are needed to elucidate the potential underlying mechanisms which will enable more effective risk stratification and development of potential therapeutic interventions to prevent cancer in CVD patients.
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Affiliation(s)
- Tanawat Attachaipanich
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Cardiac Electrophysiology Research Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
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Wang S, Wu W, Lin X, Zhang KM, Wu Q, Luo M, Zhou J. Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions. Cell Biosci 2023; 13:224. [PMID: 38041134 PMCID: PMC10693103 DOI: 10.1186/s13578-023-01171-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 11/10/2023] [Indexed: 12/03/2023] Open
Abstract
The most common site of metastasis in breast cancer is the bone, where the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation is disrupted. This imbalance causes osteolytic bone metastasis in breast cancer, which leads to bone pain, pathological fractures, spinal cord compression, and other skeletal-related events (SREs). These complications reduce patients' quality of life significantly and have a profound impact on prognosis. In this review, we begin by providing a brief overview of the epidemiology of bone metastasis in breast cancer, including current diagnostic tools, treatment approaches, and existing challenges. Then, we will introduce the pathophysiology of breast cancer bone metastasis (BCBM) and the animal models involved in the study of BCBM. We then come to the focus of this paper: a discussion of several biomarkers that have the potential to provide predictive and prognostic value in the context of BCBM-some of which may be particularly compatible with more comprehensive liquid biopsies. Beyond that, we briefly explore the potential of new technologies such as single-cell sequencing and organoid models, which will improve our understanding of tumor heterogeneity and aid in the development of improved biomarkers. The emerging biomarkers discussed hold promise for future clinical application, aiding in the prevention of BCBM, improving the prognosis of patients, and guiding the implementation of personalized medicine.
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Affiliation(s)
- Shenkangle Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
| | - Wenxin Wu
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
| | - Xixi Lin
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
| | | | - QingLiang Wu
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China
- Hangzhou Ninth People's Hospital, Hangzhou, 310014, China
| | - Mingpeng Luo
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310014, China.
| | - Jichun Zhou
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
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Wu J, Li J, Xu H, Qiu N, Huang X, Li H. Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple-negative breast cancer cells. Lipids Health Dis 2023; 22:153. [PMID: 37716956 PMCID: PMC10504790 DOI: 10.1186/s12944-023-01912-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 08/29/2023] [Indexed: 09/18/2023] Open
Abstract
BACKGROUND Adipose tissue, which is mainly composed of adipocytes, is a crucial component of the tumor microenvironment, particularly in breast cancer. Adipocytes surround breast cancer cells and may participate in cell‒cell interactions in the breast microenvironment. However, little is currently known about how adipocytes influence the biological behavior of the surrounding breast cancer cells. Hence, this study sought to investigate the role and underlying mechanisms of periostin in triple-negative breast cancer (TNBC) cells cocultured with adipogenic conditioned medium (ACM) and palmitic acid (PA). METHODS Human TNBC cell lines (MDA‒MB‒231 and SUM159PT) were treated with ACM and PA, then the expression of periostin, matrix metalloproteinases (MMPs) and stemness-related molecules were assessed by Western blotting and RT‒qPCR. The cellular viability was assessed using CCK‒8 assay. Plasmid transfection, RNA sequencing, and pathway inhibitor were used to explore the specific mechanisms of periostin. RESULTS ACM and PA elevated the expression of both MMPs and stemness-related molecules in TNBCs. MMPs can promote tumor cell infiltration and migration by degrading the extracellular matrix, and stemness expression increases the development of tumor chemoresistance. Additionally, ACM and PA increased periostin expression, while inhibiting periostin disrupted the involvement of ACM and PA in promoting extracellular matrix degradation, stemness, and chemoresistance in TNBCs. Furthermore, this study found that periostin promoted TNBC progression by activating the MAPK/ERK signaling pathway and that inhibition of MAPK/ERK signaling reduced the phenotype caused by periostin upregulation in TNBCs treated with ACM or PA. Finally, the present results showed that the high expression of POSTN, which encodes periostin, was substantially related to worse survival in TNBC patients. CONCLUSIONS The results of the study elucidated for the first time how periostin is the key protein secreted in TNBCs in response to the adipocyte-regulated tumor microenvironment, while periostin-neutralizing antibodies may serve as potential therapeutic agents in relation to TNBC progression.
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Affiliation(s)
- Jinna Wu
- Department of Breast Oncology Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China
| | - Jia Li
- Department of Breast Oncology Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China
| | - Huiya Xu
- Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Ni Qiu
- Department of Breast Oncology Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China
| | - Xiaojia Huang
- Department of Breast Oncology Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China
| | - Hongsheng Li
- Department of Breast Oncology Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China.
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Dorafshan S, Razmi M, Safaei S, Gentilin E, Madjd Z, Ghods R. Periostin: biology and function in cancer. Cancer Cell Int 2022; 22:315. [PMID: 36224629 PMCID: PMC9555118 DOI: 10.1186/s12935-022-02714-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 09/13/2022] [Indexed: 11/24/2022] Open
Abstract
Periostin (POSTN), a member of the matricellular protein family, is a secreted adhesion-related protein produced in the periosteum and periodontal ligaments. Matricellular proteins are a nonstructural family of extracellular matrix (ECM) proteins that regulate a wide range of biological processes in both normal and pathological conditions. Recent studies have demonstrated the key roles of these ECM proteins in the tumor microenvironment. Furthermore, periostin is an essential regulator of bone and tooth formation and maintenance, as well as cardiac development. Also, periostin interacts with multiple cell-surface receptors, especially integrins, and triggers signals that promote tumor growth. According to recent studies, these signals are implicated in cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, we will summarize the most current data regarding periostin, its structure and isoforms, expressions, functions, and regulation in normal and cancerous tissues. Emphasis is placed on its association with cancer progression, and also future potential for periostin-targeted therapeutic approaches will be explored.
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Affiliation(s)
- Shima Dorafshan
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mahdieh Razmi
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Sadegh Safaei
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Erica Gentilin
- Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, via G. Orus, 2b, 35129, Padua, Italy
| | - Zahra Madjd
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
| | - Roya Ghods
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
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9
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Jia L, Li G, Ma N, Zhang A, Zhou Y, Ren L, Dong D. Soluble POSTN is a novel biomarker complementing CA153 and CEA for breast cancer diagnosis and metastasis prediction. BMC Cancer 2022; 22:760. [PMID: 35831854 PMCID: PMC9281047 DOI: 10.1186/s12885-022-09864-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 07/06/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Breast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction. METHODS To assess the potential of soluble POSTN as a circulating biomarker, 242 participants, including 173 patients with different stages of BCa and 69 healthy individuals, were enrolled in this study. Soluble POSTN, together with CA153 and CEA, were determined in serum by enzyme linked immunosorbent assay (ELISA) or electrochemiluminescence immunoassays. RESULTS Serum POSTN levels in locoregional BCa patients were significantly higher than that in healthy controls. Receiver operating curve (ROC) analysis revealed that, to distinguish health controls from locoregional BCa, POSTN was observed with the highest AUC (area under curve) (AUCPOSTN = 0.72 [0.65 - 0.79], AUCCA153 = 0.57 [0.49 - 0.64], AUCCEA = 0.62 [0.55 - 0.69]), and both CA153 and CEA were observed with significantly improved AUCs by combination with POSTN (AUCPOSTN + CA153 = 0.74 [0.67 - 0.80], P < 0.001; AUCPOSTN + CEA = 0.77 [0.70 - 0.82], P < 0.001). Moreover, the performances of the POSTN were comparable with that of CA153 in predicting distant metastasis of BCa (AUCPOSTN = 0.78 [0.71 - 0.84], AUCCA153 = 0.82 [0.76 - 0.88]). Kaplan-Meier analysis indicated that elevated serum POSTN was associated with poor overall survival and progression-free survival. CONCLUSIONS This study suggested that soluble POSTN is a promising potential biomarker for diagnosis and metastasis prediction of BCa.
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Affiliation(s)
- Li Jia
- Department of Laboratory, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Guanhua Li
- Department of Anesthesiology, Chinese People's Liberation Army Rocket Force Characteristic Medical Center, Beijing, 100088, People's Republic of China
| | - Na Ma
- Cancer Biobank, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Aimin Zhang
- Department of Laboratory, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Yunli Zhou
- Department of Laboratory, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Li Ren
- Department of Laboratory, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
| | - Dong Dong
- Department of Laboratory, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
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10
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Gül D, Schweitzer A, Khamis A, Knauer SK, Ding GB, Freudelsperger L, Karampinis I, Strieth S, Hagemann J, Stauber RH. Impact of Secretion-Active Osteoblast-Specific Factor 2 in Promoting Progression and Metastasis of Head and Neck Cancer. Cancers (Basel) 2022; 14:2337. [PMID: 35565465 PMCID: PMC9106029 DOI: 10.3390/cancers14092337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/28/2022] [Accepted: 05/05/2022] [Indexed: 11/16/2022] Open
Abstract
Treatment success of head and neck cancer (HNC) is still hampered by tumor relapse due to metastases. Our study aimed to identify biomarkers by exploiting transcriptomics profiles of patient-matched metastases, primary tumors, and normal tissue mucosa as well as the TCGA HNC cohort data sets. Analyses identified osteoblast-specific factor 2 (OSF-2) as significantly overexpressed in lymph node metastases and primary tumors compared to normal tissue. High OSF-2 levels correlate with metastatic disease and reduced overall survival of predominantly HPV-negative HNC patients. No significant correlation was observed with tumor localization or therapy response. These findings were supported by the fact that OSF-2 expression was not elevated in cisplatin-resistant HNC cell lines. OSF-2 was strongly expressed in tumor-associated fibroblasts, suggesting a tumor microenvironment-promoting function. Molecular cloning and expression studies of OSF-2 variants from patients identified an evolutionary conserved bona fide protein secretion signal (1MIPFLPMFSLLLLLIVNPINA21). OSF-2 enhanced cell migration and cellular survival under stress conditions, which could be mimicked by the extracellular administration of recombinant protein. Here, OSF-2 executes its functions via ß1 integrin, resulting in the phosphorylation of PI3K and activation of the Akt/PKB signaling pathway. Collectively, we suggest OSF-2 as a potential prognostic biomarker and drug target, promoting metastases by supporting the tumor microenvironment and lymph node metastases survival rather than by enhancing primary tumor proliferation or therapy resistance.
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Affiliation(s)
- Désirée Gül
- Department of Otorhinolaryngology, Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, 55131 Mainz, Germany; (A.S.); (A.K.); (L.F.); (J.H.)
| | - Andrea Schweitzer
- Department of Otorhinolaryngology, Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, 55131 Mainz, Germany; (A.S.); (A.K.); (L.F.); (J.H.)
| | - Aya Khamis
- Department of Otorhinolaryngology, Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, 55131 Mainz, Germany; (A.S.); (A.K.); (L.F.); (J.H.)
- Oral Pathology Department, Faculty of Dentistry, Alexandria University, El Azareta, Alexandria, Egypt
| | - Shirley K. Knauer
- Institute for Molecular Biology, Centre for Medical Biotechnology (ZMB), University Duisburg-Essen, Universitätsstraße, 45117 Essen, Germany;
| | - Guo-Bin Ding
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China;
| | - Laura Freudelsperger
- Department of Otorhinolaryngology, Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, 55131 Mainz, Germany; (A.S.); (A.K.); (L.F.); (J.H.)
| | - Ioannis Karampinis
- Academic Thoracic Center, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
| | - Sebastian Strieth
- Department of Otorhinolaryngology, University Medical Center Bonn, 53127 Bonn, Germany;
| | - Jan Hagemann
- Department of Otorhinolaryngology, Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, 55131 Mainz, Germany; (A.S.); (A.K.); (L.F.); (J.H.)
| | - Roland H. Stauber
- Department of Otorhinolaryngology, Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, 55131 Mainz, Germany; (A.S.); (A.K.); (L.F.); (J.H.)
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China;
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11
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Song X, Wei C, Li X. The Signaling Pathways Associated With Breast Cancer Bone Metastasis. Front Oncol 2022; 12:855609. [PMID: 35372035 PMCID: PMC8965611 DOI: 10.3389/fonc.2022.855609] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 02/16/2022] [Indexed: 12/30/2022] Open
Abstract
Background Breast cancer (BC) is now the leading cause of cancer in women, and bone is the primary site of distant BC metastasis. BC bone metastasis seriously affects the quality of life of patients and increases the mortality rate. However, the mechanism of BC bone metastasis is not fully understood. Main Body Paget’s “seed and soil” hypothesis led experts to explore the relationship between surface markers and receptors in breast tumors and various growth factors in bone. The relevant breast tumor markers serve as “seeds”, and the bone microenvironment that is suitable for the survival of the tumor serves as the “soil”. These factors interact to make up an entire system and form feedback pathways that accelerate the production of various cytokines, attracting BC cells to migrate to bone tissue, which worsens the development of BC and seriously affects the prognosis of patients. This process is a vicious cycle. At present, there are seven major signaling pathways involved in BC bone metastasis: the OPG/RANK/RANKL signaling pathway, TGF-β signaling pathway, IGF system, PI3K-AKT-mTOR signaling pathway, Wnt signaling pathway and Hippo signaling pathway. In addition, FGF-FGFR signaling pathway, androgen-AR/LSD1-target gene pathway, Notch signaling pathway, JAK-STAT signaling pathway and CaN/NFATC1 signaling pathway also seem to be associated with BC bone metastasis. Conclusion This review focuses on the signaling pathways related to BC bone metastasis and explores the interactions among these pathways, which will lay a solid theoretical foundation for further understanding the mechanism of BC bone metastasis and developing effective targeted therapeutic drugs.
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Affiliation(s)
- Xuelian Song
- Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China
| | - Changran Wei
- Department of The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiangqi Li
- Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China
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12
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Lepucki A, Orlińska K, Mielczarek-Palacz A, Kabut J, Olczyk P, Komosińska-Vassev K. The Role of Extracellular Matrix Proteins in Breast Cancer. J Clin Med 2022; 11:jcm11051250. [PMID: 35268340 PMCID: PMC8911242 DOI: 10.3390/jcm11051250] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/16/2022] [Accepted: 02/22/2022] [Indexed: 12/12/2022] Open
Abstract
The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell–cell and cell–matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors’ action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.
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Affiliation(s)
- Arkadiusz Lepucki
- Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.L.); (K.O.)
| | - Kinga Orlińska
- Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.L.); (K.O.)
| | - Aleksandra Mielczarek-Palacz
- Department of Immunology and Serology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland; (A.M.-P.); (J.K.)
| | - Jacek Kabut
- Department of Immunology and Serology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland; (A.M.-P.); (J.K.)
| | - Pawel Olczyk
- Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.L.); (K.O.)
- Correspondence:
| | - Katarzyna Komosińska-Vassev
- Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland;
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13
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Ono J, Takai M, Kamei A, Azuma Y, Izuhara K. Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis. Biomolecules 2021; 11:1084. [PMID: 34439751 PMCID: PMC8391913 DOI: 10.3390/biom11081084] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/12/2021] [Accepted: 07/15/2021] [Indexed: 12/12/2022] Open
Abstract
Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management of type 2 inflammation and fibrotic diseases since heterogeneity is of utmost importance. Periostin expression is induced by type 2 cytokines (interleukin-4/-13) or transforming growth factor-β, and plays a vital role in the pathogenesis of allergic inflammation or interstitial lung disease, respectively, andits serum levels are correlated disease severity, prognosis and responsiveness to the treatment. We first summarise the importance of type 2 biomarker and then describe the pathological role of periostin in the development and progression of type 2 allergic inflammation and pulmonary fibrosis. In addition, then, we summarise the recent development of assay methods for periostin detection, and analyse the diseases in which periostin concentration is elevated in serum and local biological fluids and its usefulness as a biomarker. Furthermore, we describe recent findings of periostin as a biomarker in the use of biologics or anti-fibrotic therapy. Finally, we describe the factors that influence the change in periostin concentration under the healthy conditions.
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Affiliation(s)
- Junya Ono
- Shino-Test Corporation, 2-29-14 Oonodai Minami-ku, Sagamihara, Kanagawa 252-0331, Japan; (M.T.); (A.K.); (Y.A.)
| | - Masayuki Takai
- Shino-Test Corporation, 2-29-14 Oonodai Minami-ku, Sagamihara, Kanagawa 252-0331, Japan; (M.T.); (A.K.); (Y.A.)
- Division of Medical Biochemistry, Department of Biomolecular Science, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan;
| | - Ayami Kamei
- Shino-Test Corporation, 2-29-14 Oonodai Minami-ku, Sagamihara, Kanagawa 252-0331, Japan; (M.T.); (A.K.); (Y.A.)
| | - Yoshinori Azuma
- Shino-Test Corporation, 2-29-14 Oonodai Minami-ku, Sagamihara, Kanagawa 252-0331, Japan; (M.T.); (A.K.); (Y.A.)
| | - Kenji Izuhara
- Division of Medical Biochemistry, Department of Biomolecular Science, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan;
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14
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Evaluation serum levels of YKL-40, Periostin, and some inflammatory cytokines together with IL-37, a new anti-inflammatory cytokine, in patients with stable and exacerbated asthma. Heart Lung 2020; 50:177-183. [PMID: 32475627 DOI: 10.1016/j.hrtlng.2020.04.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 04/21/2020] [Accepted: 04/27/2020] [Indexed: 12/14/2022]
Abstract
INTRODUCTION As asthma has a wide range of inflammatory pathways, the researchers were focused on the markers that may be associated with exacerbation and stability in asthma. OBJECTIVE Our aim is to investigate the serum levels of some inflammatory markers and cytokines in stable and exacerbated asthmatic patients. METHODS The study included in 59 non-smoker asthma patient (Exacerbated=25, Stable=34) and 30 healthy volunteers. The serum level of periostin, YKL-40, IL-4, IL-5, IL-37, and TNF-α were detected by enzyme-linked immunosorbent assay. RESULTS Except for IL-37, the periostin, YKL-40, IL-4, IL-5, and TNF-α level in asthmatic patients were significantly higher than those of healthy control. In the exacerbated group, the periostin, YKL-40, IL-5, and TNF-α level were significantly higher than stable asthma and healthy control groups. The serum levels of IL-4 in exacerbated and stable asthma groups were significantly higher than healthy control group. There was a significant difference between IL4 levels, in stable asthma and healthy control groups. In exacerbated asthma group, IL-37 level was significantly lower than stable and healthy control groups. The highest area under the ROC curve (AUC) was found for IL-4. While there was a significant negative correlation between these parameters and FEV1, there was a positive correlation between IL-37 and FEV1, but not significant. CONCLUSIONS This study showed that increased serum periostin, YKL-40, IL-5, IL-4, and TNF-α and decreased serum IL-37 were associated with exacerbation showing uncontrolled asthma.
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15
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Sophia K, Suresh S, Sudhakar U, Abdul Cader S, Vardhini VM, Arunachalam LT, Jean SC. Comparative Evaluation of Serum and Gingival Crevicular Fluid Periostin Levels in Periodontal Health and Disease: A Biochemical Study. Cureus 2020; 12:e7218. [PMID: 32274276 PMCID: PMC7141796 DOI: 10.7759/cureus.7218] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Introduction Periostin, a secreted adhesion molecule, is a matricellular protein secreted most in periodontal ligament and periosteum. This periostin is needed for integrity and maturation of periodontal tissue. The present study was conducted to estimate and compare the gingival crevicular fluid and serum periostin levels in subjects having chronic periodontitis, gingivitis and healthy periodontium. Methods Ninety patients belonging to both sexes were categorized into three groups, 30 patients each as healthy periodontium (Group I), chronic gingivitis (Group II) and generalised chronic periodontitis (Group III). The clinical parameters included assessment of plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL). Gingival crevicular fluid (GCF) and serum samples were collected and the enzyme-linked immunosorbent assay was used to estimate periostin levels. Results Periostin levels in GCF were comparatively low in the chronic periodontitis than in the gingivitis and healthy periodontium groups and the difference was statistically significant. No statistical difference was found for serum periostin levels among Group I, Group II and Group III. On comparison of clinical parameters, significant difference was noticed among the three groups. GCF periostin levels were correlated inversely with the clinical parameters in chronic periodontitis patients. Conclusion GCF periostin levels were gradually reduced with the increase in severity of periodontal disease. This novel biomarker has role in maintaining normal periodontal tissue function and may be used as a potential marker in periodontal disease activity evaluation.
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Affiliation(s)
- Khumukcham Sophia
- Periodontics, Jawaharlal Nehru Institute of Medical Sciences, Imphal, IND
| | - Snophia Suresh
- Periodontics, Thai Moogambigai Dental College & Hospital, Chennai, IND
| | - Uma Sudhakar
- Periodontics, Thai Moogambigai Dental College & Hospital, Chennai, IND
| | - Shaik Abdul Cader
- Periodontics, Thai Moogambigai Dental College & Hospital, Chennai, IND
| | - Varsha M Vardhini
- Periodontics, Thai Moogambigai Dental College & Hospital, Chennai, IND
| | | | - S Catherine Jean
- Periodontics, Thai Moogambigai Dental College & Hospital, Chennai, IND
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16
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Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner AK. High serum levels of periostin are associated with a poor survival in breast cancer. Breast Cancer Res Treat 2020; 180:515-524. [PMID: 32040688 DOI: 10.1007/s10549-020-05570-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 02/03/2020] [Indexed: 12/21/2022]
Abstract
PURPOSE Periostin is a secreted extracellular matrix protein, which was originally described in osteoblasts. It supports osteoblastic differentiation and bone formation and has been implicated in the pathogenesis of several human malignancies, including breast cancer. However, little is known about the prognostic value of serum periostin levels in breast cancer. METHODS In this study, we analyzed serum levels of periostin in a cohort of 509 primary, non-metastatic breast cancer patients. Disseminated tumor cell (DTC) status was determined using bone marrow aspirates obtained from the anterior iliac crests. Periostin levels were stratified according to several clinical parameters and Pearson correlation analyses were performed. Kaplan-Meier survival curves were assessed by using the log-rank (Mantel-Cox) test. To identify prognostic factors, multivariate Cox regression analyses were used. RESULTS Mean serum levels of periostin were 505 ± 179 pmol/l. In older patients (> 60 years), periostin serum levels were significantly increased compared to younger patients (540 ± 184 pmol/l vs. 469 ± 167 pmol/l; p < 0.0001) and age was positively correlated with periostin expression (p < 0.0001). When stratifying the cohort according to periostin serum concentrations, the overall and breast cancer-specific mortality were significantly higher in those patients with high serum periostin (above median) compared to those with low periostin during a mean follow-up of 8.5 years (17.7% vs. 11.4% breast cancer-specific death; p = 0.03; hazard ratio 1.65). Periostin was confirmed to be an independent prognostic marker for breast cancer-specific survival (p = 0.017; hazard ratio 1.79). No significant differences in serum periostin were observed when stratifying the patients according to their DTC status. CONCLUSIONS Our findings emphasize the relevance of periostin in breast cancer and reveal serum periostin as a potential marker for disease prediction, independent on the presence of micrometastases.
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Affiliation(s)
- Tilman D Rachner
- Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany.,Center for Healthy Ageing Department of Medicine III, Technische Universität Dresden, Dresden, Germany.,German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Andy Göbel
- Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany. .,Center for Healthy Ageing Department of Medicine III, Technische Universität Dresden, Dresden, Germany. .,German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - Oliver Hoffmann
- Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Kati Erdmann
- Department of Urology, Technische Universität Dresden, Dresden, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany.,Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Sabine Kasimir-Bauer
- Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Dorit Breining
- Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany.,Center for Healthy Ageing Department of Medicine III, Technische Universität Dresden, Dresden, Germany.,German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rainer Kimmig
- Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Lorenz C Hofbauer
- Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany.,Center for Healthy Ageing Department of Medicine III, Technische Universität Dresden, Dresden, Germany.,German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ann-Kathrin Bittner
- Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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Guañabens N, Filella X, Florez H, Ruiz-Gaspá S, Conesa A, Peris P, Monegal A, Torres F. Tartrate-resistant acid phosphatase 5b, but not periostin, is useful for assessing Paget's disease of bone. Bone 2019; 124:132-136. [PMID: 31051316 DOI: 10.1016/j.bone.2019.04.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/26/2019] [Accepted: 04/27/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Periostin is a matricellular protein with a preferential location in cortical bone and periosteal tissue, and tartrate-resistant acid phosphatase 5b (TRAP5b) is a marker of osteoclast numbers. In Paget's disease of bone (PDB), there is increased cortical thickening and probably increased periosteal apposition, along with increased osteoclast numbers. OBJECTIVES To analyse if circulating periostin is a biomarker for PDB, and if it is associated with disease activity and involvement of long bones that represent major cortical contribution. Also, to analyse whether TRAP5b, a scarcely explored bone resorption marker, is useful in the assessment of PDB. PATIENTS AND METHODS We recruited 42 patients with PDB (13F/29M; 71 ± 11.6 yrs). 71.4% had active disease, 66.6% had polyostotic disease and 54.8% had long bone involvement. Blood and urine samples were taken between 8:00 and 10:00 A.M. after an overnight fast. Periostin and TRAP5b were measured in serum, using commercial ELISA assays (Biomedica and IDS, respectively). Serum total ALP, PINP, CTX, bone ALP and urinary NTX were measured. Reference values for periostin and TRAP5b were obtained from 45 healthy subjects. RESULTS Serum periostin did not differ between patients and controls (989.4 ± 173.2 vs. 966.9 ± 195.4 pMol/L, p = 0.572). No significant differences were observed between patients with and without active disease (964.5 ± 168.8 vs.1051.6 ± 175.6 pMol/L, p = 0.143), involvement or not of long bones (1022.2 ± 145.8 vs 949.7 ± 198.2 pMol/L, p = 0.181) and monostotic or polyostotic disease (963.8 ± 198.7 vs 1002.2 ± 161.4 pMol/L, p = 0.505). There were significant correlations between serum periostin and all bone turnover markers (bone ALP, PINP, uNTX, sCTX and TRAP5b) in PDB patients with active disease, but not in the inactive PDB group. Serum TRAP5b was significantly higher in PDB patients than in controls (4.43 ± 1.76 vs. 3.21 ± 1.02 U/L, p < 0.001), in those with active disease (4.98 ± 1.76 vs. 3.07 ± 0.72 U/L, p < 0.001) and in patients with polyostotic disease than in those with monostotic disease (4.81 ± 1.79 vs 3.68 ± 1.5 U/L, p = 0.005). TRAP5b levels were not influenced by previous bisphosphonate treatment (4.14 ± 1.42 vs. 4.84 ± 2.02 U/L, p = 0.206). CONCLUSIONS Periostin is not useful for assessing PDB, whilst TRAP5b, which has been a scarcely explored bone turnover marker until now, may be useful in the analysis of this disease, providing new information on the resorption process. In addition, periostin levels correlate with all classical BTMs in active PDB, suggesting that this marker may reflect periosteal and cortical metabolism in accelerated bone turnover states.
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Affiliation(s)
- Núria Guañabens
- Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, IDIBAPS, CIBERhed, University of Barcelona, Spain.
| | - Xavier Filella
- Biochemistry and Molecular Genetics Department, Hospital Clínic, Barcelona, Spain
| | - Helena Florez
- Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, IDIBAPS, CIBERhed, University of Barcelona, Spain
| | | | - Arantxa Conesa
- Department of Rheumatology, University Hospital of Castellón, Spain
| | - Pilar Peris
- Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, IDIBAPS, CIBERhed, University of Barcelona, Spain
| | - Ana Monegal
- Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, IDIBAPS, CIBERhed, University of Barcelona, Spain
| | - Ferran Torres
- Medical Statistics Core Facility, IDIBAPS, Hospital Clínic, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Spain
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The Multiaspect Functions of Periostin in Tumor Progression. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1132:125-136. [DOI: 10.1007/978-981-13-6657-4_13] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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19
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Gineyts E, Bonnet N, Bertholon C, Millet M, Pagnon-Minot A, Borel O, Geraci S, Bonnelye E, Croset M, Suhail A, Truica C, Lamparella N, Leitzel K, Hartmann D, Chapurlat R, Lipton A, Garnero P, Ferrari S, Clézardin P, Rousseau JC. The C-Terminal Intact Forms of Periostin (iPTN) Are Surrogate Markers for Osteolytic Lesions in Experimental Breast Cancer Bone Metastasis. Calcif Tissue Int 2018; 103:567-580. [PMID: 29916127 DOI: 10.1007/s00223-018-0444-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 06/14/2018] [Indexed: 12/17/2022]
Abstract
Periostin is an extracellular matrix protein that actively contributes to tumor progression and metastasis. Here, we hypothesized that it could be a marker of bone metastasis formation. To address this question, we used two polyclonal antibodies directed against the whole molecule or its C-terminal domain to explore the expression of intact and truncated forms of periostin in the serum and tissues (lung, heart, bone) of wild-type and periostin-deficient mice. In normal bones, periostin was expressed in the periosteum and specific periostin proteolytic fragments were found in bones, but not in soft tissues. In animals bearing osteolytic lesions caused by 4T1 cells, C-terminal intact periostin (iPTN) expression disappeared at the invasive front of skeletal tumors where bone-resorbing osteoclasts were present. In vitro, we found that periostin was a substrate for osteoclast-derived cathepsin K, generating proteolytic fragments that were not recognized by anti-periostin antibodies directed against iPTN. In vivo, using an in-house sandwich immunoassay aimed at detecting iPTN only, we observed a noticeable reduction of serum periostin levels (- 26%; P < 0.002) in animals bearing osteolytic lesions caused by 4T1 cells. On the contrary, this decrease was not observed in women with breast cancer and bone metastases when periostin was measured with a human assay detecting total periostin. Collectively, these data showed that mouse periostin was degraded at the bone metastatic sites, potentially by cathepsin K, and that the specific measurement of iPTN in serum should assist in detecting bone metastasis formation in breast cancer.
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Affiliation(s)
- Evelyne Gineyts
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Nicolas Bonnet
- Division of Bone Diseases, Geneva University Hospital, Geneva, Switzerland
| | - Cindy Bertholon
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Marjorie Millet
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | | | - Olivier Borel
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
- Rheumatology Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Sandra Geraci
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Edith Bonnelye
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Martine Croset
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Ali Suhail
- Penn State Hershey Medical Center, Hershey, PA, USA
| | | | | | - Kim Leitzel
- Penn State Hershey Medical Center, Hershey, PA, USA
| | | | - Roland Chapurlat
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
- Rheumatology Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Allan Lipton
- Penn State Hershey Medical Center, Hershey, PA, USA
| | - Patrick Garnero
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Serge Ferrari
- Division of Bone Diseases, Geneva University Hospital, Geneva, Switzerland
| | - Philippe Clézardin
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France
| | - Jean-Charles Rousseau
- INSERM 1033, Pavillon F, Hôpital Edouard Herriot, Lyon, 69437, France.
- Univ. Lyon, UFR de Médecine Lyon-Est, Lyon, France.
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González-González L, Alonso J. Periostin: A Matricellular Protein With Multiple Functions in Cancer Development and Progression. Front Oncol 2018; 8:225. [PMID: 29946533 PMCID: PMC6005831 DOI: 10.3389/fonc.2018.00225] [Citation(s) in RCA: 189] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 05/30/2018] [Indexed: 01/19/2023] Open
Abstract
Tumor microenvironment is considered nowadays as one of the main players in cancer development and progression. Tumor microenvironment is highly complex and consists of non-tumor cells (i.e., cancer-associated fibroblast, endothelial cells, or infiltrating leukocytes) and a large list of extracellular matrix proteins and soluble factors. The way that microenvironment components interact among them and with the tumor cells is very complex and only partially understood. However, it is now clear that these interactions govern and modulate many of the cancer hallmarks such as cell proliferation, the resistance to death, the differentiation state of tumor cells, their ability to migrate and metastasize, and the immune response against tumor cells. One of the microenvironment components that have emerged in the last years with strength is a heterogeneous group of multifaceted proteins grouped under the name of matricellular proteins. Matricellular proteins are a family of non-structural matrix proteins that regulate a variety of biological processes in normal and pathological situations. Many components of this family such as periostin (POSTN), osteopontin (SPP1), or the CNN family of proteins have been shown to regulate key aspect of tumor biology, including proliferation, invasion, matrix remodeling, and dissemination to pre-metastatic niches in distant organs. Matricellular proteins can be produced by tumor cells themselves or by tumor-associated cells, and their synthesis can be affected by intrinsic and/or extrinsic tumor cell factors. In this review, we will focus on the role of POSTN in the development and progression of cancer. We will describe their functions in normal tissues and the mechanisms involved in their regulation. We will analyze the tumors in which their expression is altered and their usefulness as a biomarker of tumor progression. Finally, we will speculate about future directions for research and therapeutic approaches targeting POSTN.
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Affiliation(s)
- Laura González-González
- Unidad de Tumores Sólidos Infantiles, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain
| | - Javier Alonso
- Unidad de Tumores Sólidos Infantiles, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain
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21
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Li C, Xu J, Wang Q, Geng S, Yan Z, You J, Li Z, Zou X. Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy. Oncol Lett 2018; 15:8072-8078. [PMID: 29725485 DOI: 10.3892/ol.2018.8310] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 12/08/2017] [Indexed: 12/22/2022] Open
Abstract
The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.
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Affiliation(s)
- Changyou Li
- Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Jing Xu
- Department of Pathology, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Qi Wang
- Department of Pathology, Qingdao Cancer Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Shaoqing Geng
- Department of Pathology, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Zheng Yan
- Department of Breast Surgery, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Jin You
- Anorectal Department, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Zhenfeng Li
- Department of Breast Surgery, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
| | - Xiao Zou
- Department of Breast Surgery, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P.R. China
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Tan CC, Li GX, Tan LD, Du X, Li XQ, He R, Wang QS, Feng YM. Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction. Oncotarget 2018; 7:79688-79705. [PMID: 27806311 PMCID: PMC5346745 DOI: 10.18632/oncotarget.12939] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 09/25/2016] [Indexed: 11/25/2022] Open
Abstract
Bone is one of the most common organs of breast cancer metastasis. Cancer cells that mimic osteoblasts by expressing bone matrix proteins and factors have a higher likelihood of metastasizing to bone. However, the molecular mechanisms of osteomimicry formation of cancer cells remain undefined. Herein, we identified a set of bone-related genes (BRGs) that are ectopically co-expressed in primary breast cancer tissues and determined that osteomimetic feature is obtained due to the osteoblast-like transformation of epithelial breast cancer cells that have undergone epithelial-mesenchymal transition (EMT) followed by bone morphogenetic protein-2 (BMP2) stimulation. Furthermore, we demonstrated that breast cancer cells that transformed into osteoblast-like cells with high expression of BRGs showed enhanced chemotaxis, adhesion, proliferation and multidrug resistance in an osteoblast-mimic bone microenvironment in vitro. During these processes, runt-related transcription factor 2 (RUNX2) functioned as a master mediator by suppressing or activating the transcription of BRGs that underlie the dynamic antagonism between the TGF-β/SMAD and BMP/SMAD signaling pathways in breast cancer cells. Our findings suggest a novel mechanism of osteomimicry formation that arises in primary breast tumors, which may explain the propensity of breast cancer to metastasize to the skeleton and contribute to potential strategies for predicting and targeting breast cancer bone metastasis and multidrug resistance.
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Affiliation(s)
- Cong-Cong Tan
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Gui-Xi Li
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Li-Duan Tan
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Xin Du
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Xiao-Qing Li
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.,Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Rui He
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Qing-Shan Wang
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.,Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
| | - Yu-Mei Feng
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.,Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China
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23
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Kim GE, Lee JS, Park MH, Yoon JH. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. PLoS One 2017; 12:e0187635. [PMID: 29161296 PMCID: PMC5697858 DOI: 10.1371/journal.pone.0187635] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Accepted: 10/23/2017] [Indexed: 01/08/2023] Open
Abstract
Invasion and metastasis are direct causes of mortality in patients with breast cancer and require reciprocal interactions between cancer cells and the extracellular matrix (ECM). Periostin, a fasciclin-containing adhesive ECM glycoprotein, is frequently overexpressed in various types of human cancer, and its overexpression in cancer-associated stroma and/or cancer cells is usually associated with poor clinical outcomes. However, the expression of periostin in the successive steps of breast tumorigenesis and its association with outcome variables have not been well established in breast carcinoma. The present study aimed to assess the role of periostin alteration in breast tumorigenesis and evaluate the putative prognostic value of periostin as a function of its compartmentalization. Immunohistochemical staining with anti-periostin antibody was performed in a total of 300 patients (26 patients with normal breast tissues, 76 patients with ductal carcinoma in situ [DCIS], and 198 patients with invasive breast carcinoma [IBC]) using tissue microarray. Periostin immunoreactivity was assessed in both epithelial tissue and the surrounding stromal compartment. The mRNA and protein expression of periostin were analyzed in 10 paired normal/invasive cancer frozen specimens by quantitative real time-polymerase chain reaction and western blot analysis, respectively. In cancer tissues, periostin mRNA and protein expression were increased compared with adjacent normal tissues. Both epithelial and stromal periostin staining scores significantly increased in a stepwise manner with disease progression from normal breast tissue to DCIS and IBC (P = 0.000 and 0.000, respectively). High epithelial and stromal periostin expression was observed in 109/189 (57.7%) and 158/189 (83.6%) cases of IBC, respectively. High epithelial periostin expression was more frequently observed in the distant metastatic relapse-positive group than in the distant metastatic relapse-negative group (41/51 [80.4%] vs. 68/138 [49.3%] cases [P = 0.000]). Furthermore, high epithelial periostin expression was associated with reduced disease-free survival and overall survival in univariate and multivariate analysis. Periostin may play an important role in the progression of breast tumor, and epithelial periostin expression may serve as a new parameter for prediction of prognosis in patients with IBC. Further studies examining periostin expression and its potential as a target of IBC therapy are warranted.
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Affiliation(s)
- Ga-Eon Kim
- Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Ji Shin Lee
- Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
- * E-mail:
| | - Min Ho Park
- Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Jung Han Yoon
- Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea
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24
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Landry NM, Cohen S, Dixon IMC. Periostin in cardiovascular disease and development: a tale of two distinct roles. Basic Res Cardiol 2017; 113:1. [PMID: 29101484 DOI: 10.1007/s00395-017-0659-5] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 10/12/2017] [Indexed: 12/18/2022]
Abstract
Tissue development and homeostasis are dependent upon the concerted synthesis, maintenance, and degradation of extracellular matrix (ECM) molecules. Cardiac fibrosis is now recognized as a primary contributor to incidence of heart failure, particularly heart failure with preserved ejection fraction, wherein cardiac filling in diastole is compromised. Periostin is a cell-associated protein involved in cell fate determination, proliferation, tumorigenesis, and inflammatory responses. As a non-structural component of the ECM, secreted 90 kDa periostin is emerging as an important matricellular factor in cardiac mesenchymal tissue development. In addition, periostin's role as a mediator in cell-matrix crosstalk has also garnered attention for its association with fibroproliferative diseases in the myocardium, and for its association with TGF-β/BMP signaling. This review summarizes the phylogenetic history of periostin, its role in cardiac development, and the major signaling pathways influencing its expression in cardiovascular pathology. Further, we provide a synthesis of the current literature to distinguish the multiple roles of periostin in cardiac health, development and disease. As periostin may be targeted for therapeutic treatment of cardiac fibrosis, these insights may shed light on the putative timing for application of periostin-specific therapies.
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Affiliation(s)
- Natalie M Landry
- Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, Canada
| | - Smadar Cohen
- Regenerative Medicine and Stem Cell Research Center, Ilse Katz Institute for Nanoscale Science and Technology, Beersheba, Israel.,Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Ian M C Dixon
- Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, Canada. .,Laboratory of Molecular Cardiology, St. Boniface Hospital Albrechtsen Research Centre, R3010-351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada.
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Ye D, Shen ZS, Qiu SJ, Li Q, Wang GL. Role and underlying mechanisms of the interstitial protein periostin in the diagnosis and treatment of malignant tumors. Oncol Lett 2017; 14:5099-5106. [PMID: 29142596 DOI: 10.3892/ol.2017.6866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 11/23/2016] [Indexed: 12/16/2022] Open
Abstract
Invasion and metastasis are the major characteristics of malignant tumors and are complex processes involving multiple genes. Gene regulation is a precise, large and complex biological control system, and its underlying mechanisms remain to be elucidated. Mesenchymal-specific genes are expressed primarily by mesenchymal cells, and the expression products of these genes are molecules with various structures and functions, including secreted proteins and extracellular matrix proteins. The periostin gene has been newly identified as a mesenchymal-specific gene and an extracellular-matrix secreted protein. Periostin is able to bind to various subtypes of integrin receptors on the surface of the cell membrane. This triggers relevant signal transduction pathways to alter the microenvironment of cancer cells in order to facilitate their survival, invasion, metastasis and angiogenesis as well as enhance the tolerance to hypoxia and chemicals. Therefore, periostin is associated with the grade of malignancy, level of invasion and prognosis of malignant tumors. The in-depth study of periostin may provide an effective marker for tumor diagnosis and prognosis, as well as a novel treatment target.
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Affiliation(s)
- Dong Ye
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
| | - Zhi Sen Shen
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
| | - Shi Jie Qiu
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
| | - Qun Li
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
| | - Guo Li Wang
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
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Zhang Y, Yuan D, Yao Y, Sun W, Shi Y, Su X. Predictive and prognostic value of serum periostin in advanced non-small cell lung cancer patients receiving chemotherapy. Tumour Biol 2017; 39:1010428317698367. [PMID: 28459197 DOI: 10.1177/1010428317698367] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Periostin is an extracellular matrix protein involved in tumorigenesis and metastasis. However, the role of serum periostin as a surrogate marker for treatment efficacy is still unknown. In 122 advanced non-small cell lung cancer cases, 37 patients with benign lung disease and 40 healthy controls, serum periostin was measured by enzyme-linked immunosorbent assays. The associations of serum periostin levels with the clinic-pathological parameters, chemotherapy response, and clinical outcomes of non-small cell lung cancer patients were analyzed. Serum periostin levels were significantly higher in non-small cell lung cancer patients, and it was related significantly to bone metastasis ( p = 0.021). Serum periostin of 65 non-small cell lung cancer patients were detected before and after two cycles of chemotherapy. The patients with and without periostin response had significant difference in objective response to chemotherapy ( p = 0.001). For the 122 non-small cell lung cancer patients, the median progression-free survival was 5 months. In a multivariate analysis, performance status (hazard ratio, 1.71; 95% confidence interval, 1.10-2.67), baseline periostin (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01), and periostin response (hazard ratio, 0.50; 95% confidence interval, 0.29-0.86) were significantly correlated with prognosis. In conclusion, serum periostin was elevated in advanced non-small cell lung cancer patients. Baseline periostin and periostin responses appeared to be reliable surrogate markers to predict chemotherapy response and survival in patients with advanced non-small cell lung cancer.
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Affiliation(s)
- Yan Zhang
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Dongmei Yuan
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Yanwen Yao
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Wenkui Sun
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Yi Shi
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Xin Su
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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Procházková I, Lenčo J, Fučíková A, Dresler J, Čápková L, Hrstka R, Nenutil R, Bouchal P. Targeted proteomics driven verification of biomarker candidates associated with breast cancer aggressiveness. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 2017; 1865:488-498. [PMID: 28216224 DOI: 10.1016/j.bbapap.2017.02.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 01/07/2017] [Accepted: 02/15/2017] [Indexed: 02/07/2023]
Abstract
Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics. Here we verified these findings in the same set of 96 tumors using targeted proteomics based on selected reaction monitoring with mTRAQ labeling (mTRAQ-SRM), transcriptomics and immunohistochemistry and validated in 5 independent sets of 715 patients using transcriptomics. We confirmed: (i) positive association of anterior gradient protein 2 homolog (AGR2) and periostin (POSTN) and negative association of annexin A1 (ANXA1) with estrogen receptor status; (ii) positive association of stathmin (STMN1), cofilin-1 (COF1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1) and negative associations of thrombospondin-2 (TSP2) and POSTN levels with tumor grade; and (iii) positive association of POSTN, alpha-actinin-4 (ACTN4) and STMN1 with lymph node status. This study highlights a panel of gene products that can contribute to breast cancer aggressiveness and metastasis, the understanding of which is important for development of more precise breast cancer treatment.
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Affiliation(s)
- Iva Procházková
- Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 65653 Brno, Czech Republic; Masaryk University, Faculty of Science, Department of Biochemistry, Kotlarska 2, 61137 Brno, Czech Republic
| | - Juraj Lenčo
- University of Defence, Faculty of Military Health Sciences, Department of Molecular Pathology and Biology, Trebesska 1575, 50001 Hradec Kralove, Czech Republic
| | - Alena Fučíková
- University of Defence, Faculty of Military Health Sciences, Department of Molecular Pathology and Biology, Trebesska 1575, 50001 Hradec Kralove, Czech Republic
| | - Jiří Dresler
- University of Defence, Faculty of Military Health Sciences, Department of Molecular Pathology and Biology, Trebesska 1575, 50001 Hradec Kralove, Czech Republic; Military Health Institute, Tychonova 1, 160 00 Prague, Czech Republic
| | - Lenka Čápková
- Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 65653 Brno, Czech Republic; Masaryk University, Faculty of Science, Department of Biochemistry, Kotlarska 2, 61137 Brno, Czech Republic
| | - Roman Hrstka
- Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 65653 Brno, Czech Republic
| | - Rudolf Nenutil
- Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 65653 Brno, Czech Republic
| | - Pavel Bouchal
- Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 65653 Brno, Czech Republic; Masaryk University, Faculty of Science, Department of Biochemistry, Kotlarska 2, 61137 Brno, Czech Republic.
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Zheng Q, Lu J, Li R, Hu C, Liu P. Elevated periostin in serum and peritoneal washing fluids as potential biomarkers for endometriosis. Gynecol Endocrinol 2016; 32:900-903. [PMID: 27251862 DOI: 10.1080/09513590.2016.1190329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND To identify the level of periostin in serum and peritoneal washing fluids (PWF) from women with and without endometriosis, as well as to explore the potential of periostin as a biomarker of endometriosis. METHODS Samples were obtained from 184 women with and without endometriosis. Concentrations of periostin in PWF and blood were measured by enzyme-linked immunosorbent assay. RESULTS Levels of periostin both in serum and PWF were notably elevated in women with endometriosis in both the proliferative and secretory phase. Combined with dysmenorrhea and infertility, two potential covariates, the serum periostin had a sensitivity of 75.00%, specificity of 65.00%, and area under the curve (AUC) of 0.774, whereas the PWF periostin had a sensitivity of 94.23%, specificity of 90.00%, and AUC of 0.967 for the diagnosis of endometriosis. CONCLUSION Serum and PWF periostin concentrations may be new potential biomarkers for endometriosis, especially when combined with dysmenorrhea and infertility.
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Affiliation(s)
- Qiaomei Zheng
- a Department of Obstetrics and Gynecology , Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Jingjing Lu
- a Department of Obstetrics and Gynecology , Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Rui Li
- a Department of Obstetrics and Gynecology , Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Chen Hu
- a Department of Obstetrics and Gynecology , Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Peishu Liu
- a Department of Obstetrics and Gynecology , Qilu Hospital of Shandong University , Jinan , People's Republic of China
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Li K, Kang H, Wang Y, Hai T, Rong G, Sun H. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology. Med Oncol 2016; 33:64. [PMID: 27235140 DOI: 10.1007/s12032-016-0779-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2016] [Accepted: 05/17/2016] [Indexed: 12/15/2022]
Abstract
Accumulating evidence suggests that carcinoma-associated fibroblasts (CAFs) influence the efficacy of endocrine therapy. Aromatase inhibitors inhibit the growth of breast tumors by inhibiting the synthesis of estrogen. However, it remains unknown whether the aromatase inhibitor letrozole has an additional impact on CAFs, which further influence the efficacy of endocrine therapy. Primary CAFs were isolated from primary estrogen receptor-positive human breast tumors. Estrogen-deprived culture medium was used to exclude the influence of steroids. In co-culture, primary cultured CAFs increased MCF7 cell adhesion, invasion, migration and proliferation, and letrozole treatment inhibited these increases, except for the increase in proliferation. In total, 258 up-regulated genes and 47 down-regulated genes with an absolute fold change >2 were identified in CAFs co-cultured with MCF7 cell after letrozole treatment. One up-regulated genes (POSTN) and seven down-regulated genes (CCL2, CCL5, CXCL1, IL-8, CXCL5, LEP and NGF) were further validated by real-time PCR. The changes in CCL2 and CXCL1 expression were further confirmed using an automated microscopic imaging-based, high content analysis platform. Although the results need further functional validation, this study is the first to describe the differential tumor-promoting phenotype of CAFs induced by letrozole and the associated gene expression alterations. Most importantly, our data revealed that down-regulation of several secreted factors (CCL2, CCL5, CXCL1 etc.) in CAFs might be partially responsible for the efficacy of letrozole.
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Affiliation(s)
- Kaifu Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Hua Kang
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China.
| | - Yajun Wang
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Tao Hai
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Guohua Rong
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Haichen Sun
- Surgery Lab, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China
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Cobo T, Viloria CG, Solares L, Fontanil T, González-Chamorro E, De Carlos F, Cobo J, Cal S, Obaya AJ. Role of Periostin in Adhesion and Migration of Bone Remodeling Cells. PLoS One 2016; 11:e0147837. [PMID: 26809067 PMCID: PMC4725750 DOI: 10.1371/journal.pone.0147837] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 01/08/2016] [Indexed: 12/27/2022] Open
Abstract
Periostin is an extracellular matrix protein highly expressed in collagen-rich tissues subjected to continuous mechanical stress. Functionally, periostin is involved in tissue remodeling and its altered function is associated to numerous pathological processes. In orthodontics, periostin plays key roles in the maintenance of dental tissues and it is mainly expressed in those areas where tension or pressing forces are taking place. In this regard, high expression of periostin is essential to promote migration and proliferation of periodontal ligament fibroblasts. However little is known about the participation of periostin in migration and adhesion processes of bone remodeling cells. In this work we employ the mouse pre-osteoblastic MC3T3-E1 and the macrophage-like RAW 264.7 cell lines to overexpress periostin and perform different cell-based assays to study changes in cell behavior. Our data indicate that periostin overexpression not only increases adhesion capacity of MC3T3-E1 cells to different matrix proteins but also hampers their migratory capacity. Changes on RNA expression profile of MC3T3-E1 cells upon periostin overexpression have been also analyzed, highlighting the alteration of genes implicated in processes such as cell migration, adhesion or bone metabolism but not in bone differentiation. Overall, our work provides new evidence on the impact of periostin in osteoblasts physiology.
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Affiliation(s)
- Teresa Cobo
- Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Cristina G. Viloria
- Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Laura Solares
- Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Tania Fontanil
- Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Elena González-Chamorro
- Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Félix De Carlos
- Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Juan Cobo
- Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Santiago Cal
- Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
- Instituto Universitario de Oncología (IUOPA), Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Alvaro J. Obaya
- Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
- Instituto Universitario de Oncología (IUOPA), Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
- * E-mail:
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Trotter TN, Yang Y. Matricellular proteins as regulators of cancer metastasis to bone. Matrix Biol 2016; 52-54:301-314. [PMID: 26807761 DOI: 10.1016/j.matbio.2016.01.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 01/19/2016] [Accepted: 01/19/2016] [Indexed: 01/08/2023]
Abstract
Metastasis is the major cause of death in cancer patients, and a frequent site of metastasis for many cancers is the bone marrow. Therefore, understanding the mechanisms underlying the metastatic process is necessary for future prevention and treatment. The tumor microenvironment is now known to play a role in the metastatic cascade, both at the primary tumor and in metastatic sites, and includes both cellular and non-cellular components. The extracellular matrix (ECM) provides structural support and signaling cues to cells. One particular group of molecules associated with the ECM, known as matricellular proteins, modulate multiple aspects of tumor biology, including growth, migration, invasion, angiogenesis and metastasis. These proteins are also important for normal function in the bone by regulating bone formation and bone resorption. Recent studies have described a link between some of these proteins and metastasis of various tumors to the bone. The aim of this review is to summarize what is currently known about matricellular protein influence on bone metastasis. Particular attention to the contribution of both tumor cells and non-malignant cells in the bone has been given.
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Affiliation(s)
- Timothy N Trotter
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Yang Yang
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States; Comprehensive Cancer Center and the Center for Metabolic Bone Disease, University of Alabama at Birmingham, Birmingham, AL, United States.
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Kim BJ, Rhee Y, Kim CH, Baek KH, Min YK, Kim DY, Ahn SH, Kim H, Lee SH, Lee SY, Kang MI, Koh JM. Plasma periostin associates significantly with non-vertebral but not vertebral fractures in postmenopausal women: Clinical evidence for the different effects of periostin depending on the skeletal site. Bone 2015; 81:435-441. [PMID: 26297442 DOI: 10.1016/j.bone.2015.08.014] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Revised: 07/28/2015] [Accepted: 08/17/2015] [Indexed: 12/22/2022]
Abstract
BACKGROUND Periostin is preferentially expressed by the periosteum, which mainly covers the long bones. Therefore, the role of periostin in osteoporotic fracture (OF) may differ depending on bone type. We performed a case-control study to investigate whether periostin can serve as a predictor of OF risk, particularly after dividing OFs into non-vertebral and vertebral fractures. METHODS Among 532 consecutive postmenopausal women not taking any drug or without any disease that could affect bone metabolism, 133 cases with OF (i.e., non-vertebral and/or vertebral fractures) and 133 age- and body mass index-matched controls were enrolled. Non-vertebral (i.e., forearm, humerus, hip, and pelvis; n=81) and morphological vertebral (n=62) fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma periostin levels were also measured. RESULTS Plasma periostin was markedly higher in subjects with non-vertebral fracture than their controls even after adjustment for BMD and potential confounders (P=0.006). Each standard deviation increment of plasma periostin was associated with a multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds for non-vertebral fracture were 2.48-fold higher in subjects in the highest periostin tertile compared with those in the lowest periostin tertile (95% confidence interval=1.10-5.61). However, associations between plasma periostin and vertebral fracture were not observed, regardless of the adjustment model used. Consistently, plasma periostin levels were inversely associated with proximal femur BMD (P=0.007 to 0.030) but not lumbar spine BMD. In subgroup analyses, plasma periostin had no correlation with the levels of classical bone turnover markers. CONCLUSIONS Plasma periostin may be a potential biomarker of the risk of OF, especially in non-spinal skeletal sites, such as the limbs, rather than spine.
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Affiliation(s)
- Beom-Jun Kim
- Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Yumie Rhee
- Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea
| | - Chong Hwa Kim
- Department of Internal Medicine, Sejong General Hospital, Bucheon 422-711, Republic of Korea
| | - Ki Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul 137-701, Republic of Korea
| | - Yong-Ki Min
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea
| | - Deog-Yoon Kim
- Department of Nuclear Medicine, Kyunghee University School of Medicine, Seoul 130-872, Republic of Korea
| | - Seong Hee Ahn
- Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Hyeonmok Kim
- Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Seung Hun Lee
- Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Sun-Young Lee
- Asan Institute for Life Sciences, Seoul 138-736, Republic of Korea
| | - Moo-Il Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul 137-701, Republic of Korea.
| | - Jung-Min Koh
- Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
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Venning FA, Wullkopf L, Erler JT. Targeting ECM Disrupts Cancer Progression. Front Oncol 2015; 5:224. [PMID: 26539408 PMCID: PMC4611145 DOI: 10.3389/fonc.2015.00224] [Citation(s) in RCA: 195] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 09/30/2015] [Indexed: 12/18/2022] Open
Abstract
Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.
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Affiliation(s)
- Freja A. Venning
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark
| | - Lena Wullkopf
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark
| | - Janine T. Erler
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark
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Padial-Molina M, Volk SL, Rios HF. Preliminary insight into the periostin leverage during periodontal tissue healing. J Clin Periodontol 2015. [PMID: 26202398 DOI: 10.1111/jcpe.12432] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tissue repair and regeneration is assisted by the efficient coordination of cell and extracellular matrix interactions mediated by matricellular molecules such as periostin. Given its high expression around the teeth, the periodontal organ represents an ideal system to capture the protein dynamics during wound healing. METHODS An observational prospective case-control study was designed to characterize periostin changes over time after periodontal surgery in tissue, oral fluids and serum by histological, protein and mRNA analyses. RESULTS Histological analysis showed lower periostin with a diffuse local distribution pattern in disease patients. Levels of periostin in gingival crevicular fluid (GCF) increased over time for both groups, more noticeably in the periodontitis subjects. A transient and subtle change in circulating periostin levels was also noticed. The mRNA periostin levels contrasted with the protein levels and may indicate the underlying post-transcriptional regulatory process during chronic inflammation. Levels of known periodontal disease biomarkers such as IL-β, IL1-α, TNF-α, MIP-1α and CRP served as tissue stability markers and complemented the clinical parameters recorded. CONCLUSION The transient local increase in GCF periostin after eliminating the local etiology in periodontally affected sites suggests its importance in the maturation and stability of the connective tissue. The decreasing levels observed as the tissue healed highlight its spatial/temporal significance.
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Affiliation(s)
- Miguel Padial-Molina
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.,Department of Oral Surgery and Implant Dentistry, School of Dentistry, University of Granada, Granada, Spain
| | - Sarah L Volk
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Hector F Rios
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
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Nuzzo PV, Rubagotti A, Argellati F, Di Meglio A, Zanardi E, Zinoli L, Comite P, Mussap M, Boccardo F. Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa). Int J Mol Sci 2015; 16:17181-92. [PMID: 26225965 PMCID: PMC4581188 DOI: 10.3390/ijms160817181] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 07/14/2015] [Accepted: 07/17/2015] [Indexed: 01/08/2023] Open
Abstract
PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.
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Affiliation(s)
- Pier Vitale Nuzzo
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
- Department of Medicine, School of Medicine, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Alessandra Rubagotti
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
- Department of Medicine, School of Medicine, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Francesca Argellati
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Antonio Di Meglio
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
- Department of Medicine, School of Medicine, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Elisa Zanardi
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
- Department of Medicine, School of Medicine, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Linda Zinoli
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Paola Comite
- Department of Laboratory Medicine, IRCCS San Martino University Hospital-IST National Cancer Research Institute Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Michele Mussap
- Department of Laboratory Medicine, IRCCS San Martino University Hospital-IST National Cancer Research Institute Largo Rosanna Benzi 10, 16132 Genoa, Italy.
| | - Francesco Boccardo
- Academic Unit of Medical Oncology, IRCCS San Martino University Hospital-IST National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
- Department of Medicine, School of Medicine, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
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Sonnenberg-Riethmacher E, Miehe M, Riethmacher D. Promotion of periostin expression contributes to the migration of Schwann cells. J Cell Sci 2015; 128:3345-55. [PMID: 26187852 DOI: 10.1242/jcs.174177] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 06/25/2015] [Indexed: 12/15/2022] Open
Abstract
Neuregulin ligands and their ErbB receptors are important for the development of Schwann cells, the glial cells of the peripheral nervous system (PNS). ErbB3 deficiency is characterized by a complete loss of Schwann cells along axons of the peripheral nerves, impaired fasciculation and neuronal cell death. We performed comparative gene expression analysis of dorsal root ganglia (DRG) explant cultures from ErbB3-deficient and wild-type mice in order to identify genes that are involved in Schwann cell development and migration. The extracellular matrix (ECM) gene periostin was found to exhibit the most prominent down regulation in ErbB3-deficient DRG. Expression analysis revealed that the periostin-expressing cell population in the PNS corresponds to Schwann cell precursors and Schwann cells, and is particularly high in migratory Schwann cells. Furthermore, stimulation of Schwann cells with neuregulin-1 (NRG1) or transforming growth factor β (TGFβ-1) resulted in an upregulation of periostin expression. Interestingly, DRG explant cultures of periostin-deficient mice revealed a significant reduction of the number of migrating Schwann cells. These data demonstrate that the expression of periostin is stimulated by ErbB ligand NRG1 and influences the migration of Schwann cell precursors.
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Affiliation(s)
- Eva Sonnenberg-Riethmacher
- Human Development and Health, University of Southampton, School of Medicine, Tremona Road, Southampton SO16 6YD, UK Center for Molecular Neurobiology, University of Hamburg, Falkenried 94, Hamburg 20251, Germany
| | - Michaela Miehe
- Center for Molecular Neurobiology, University of Hamburg, Falkenried 94, Hamburg 20251, Germany Institut for Immunological Engineering, University of Aarhus, Gustav Wieds Vej 10, Aarhus C 8000, Denmark
| | - Dieter Riethmacher
- Human Development and Health, University of Southampton, School of Medicine, Tremona Road, Southampton SO16 6YD, UK Center for Molecular Neurobiology, University of Hamburg, Falkenried 94, Hamburg 20251, Germany
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Heidari P, Esfahani SA, Turker NS, Wong G, Wang TC, Rustgi AK, Mahmood U. Imaging of Secreted Extracellular Periostin, an Important Marker of Invasion in the Tumor Microenvironment in Esophageal Cancer. J Nucl Med 2015; 56:1246-51. [PMID: 26069303 DOI: 10.2967/jnumed.115.156216] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 05/28/2015] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED Periostin, an extracellular matrix protein, plays key role in cell adhesion and motility within the tumor microenvironment and is correlated with tumor invasion. We developed and characterized a PET tracer that specifically targets periostin and evaluated the probe in preclinical models of esophageal squamous cell carcinoma (ESCC). METHODS The Institutional Animal Care and Use Committee approved all animal studies. Antiperiostin-F(ab')2 was generated from a monoclonal antibody by enzymatic digestion, conjugated to DOTA, and labeled with (64)Cu. Human ESCC cell lines, TE-11 with high and TT with minimal periostin expression, were implanted in nu/nu mice to generate the positive and control tumor models, respectively. PET/CT imaging was performed at 6, 12, and 24 h and organ-specific biodistribution at 24 h after probe injection. Additionally the probe was tested in a genetically engineered mouse model of periostin-expressing distal esophageal/forestomach ESCC. Tissue microarrays of esophageal neoplasms and ESCC as well as extracted tumor samples were stained for periostin. RESULTS We generated a (64)Cu-DOTA-anti-periostin-F(ab')2 with a dissociation constant of 29.2 ± 3.0 nM. PET/CT images and biodistribution studies showed significantly higher tracer uptake in TE-11 than TT tumors (maximum standardized uptake value, 24 h: 0.67 ± 0.09 vs. 0.36 ± 0.03, P < 0.0005; percentage injected dose per gram, 24 h: 3.24 ± 0.65 vs. 1.63 ± 0.49, P < 0.0001). In genetically engineered mouse models, ESCC high periostin tracer uptake anatomically correlated with the (18)F-FDG uptake at the gastroesophageal junction. All of the ESCC cores and 96.2% of adenocarcinoma stained positive for periostin, with most stained strongly (67.3% and 69.3%, respectively). CONCLUSION We demonstrated that specific imaging of extracellular matrix periostin in ESCC is feasible using a targeted PET tracer. Detection of periostin in the tumor microenvironment may help with early detection, postsurgical follow-up, and in situ characterization of primary and metastatic lesions.
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Affiliation(s)
- Pedram Heidari
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts
| | - Shadi A Esfahani
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts
| | - Nazife S Turker
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts
| | - Gabrielle Wong
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York; and
| | - Timothy C Wang
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Anil K Rustgi
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York; and
| | - Umar Mahmood
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts
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Honsawek S, Wilairatana V, Udomsinprasert W, Sinlapavilawan P, Jirathanathornnukul N. Association of plasma and synovial fluid periostin with radiographic knee osteoarthritis: Cross-sectional study. Joint Bone Spine 2015; 82:352-5. [PMID: 25881760 DOI: 10.1016/j.jbspin.2015.01.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 01/28/2015] [Indexed: 01/13/2023]
Abstract
OBJECTIVE To investigate plasma and synovial fluid (SF) periostin of knee osteoarthritis (OA) patients and to determine the relationship between periostin levels and the radiographic severity. METHODS A total of 110 subjects (90 knee OA patients and 20 healthy controls) were enrolled in this study. Plasma and SF periostin were examined using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren-Lawrence classification. RESULTS Although plasma periostin was greater in OA patients than in controls, the difference was not significant. Additionally, SF periostin was significantly higher with respect to paired plasma (P<0.001). Moreover, plasma and SF periostin demonstrated significantly positive correlation with the radiographic severity of knee OA (r=0.537, P<0.001 and r=0.427, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and SF periostin (r=0.368, P<0.001). CONCLUSIONS Plasma and SF periostin levels were positively correlated with the radiographic severity of knee OA.
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Affiliation(s)
- Sittisak Honsawek
- Department of Biochemistry and Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873, Rama IV road, Patumwan, 10330 Bangkok, Thailand; Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 10330 Bangkok, Thailand.
| | - Vajara Wilairatana
- Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 10330 Bangkok, Thailand
| | - Wanvisa Udomsinprasert
- Department of Biochemistry and Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873, Rama IV road, Patumwan, 10330 Bangkok, Thailand
| | - Peerasit Sinlapavilawan
- Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 10330 Bangkok, Thailand
| | - Napaphat Jirathanathornnukul
- Department of Biochemistry and Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873, Rama IV road, Patumwan, 10330 Bangkok, Thailand
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Liu GX, Xi HQ, Sun XY, Wei B. Role of periostin and its antagonist PNDA-3 in gastric cancer metastasis. World J Gastroenterol 2015; 21:2605-2613. [PMID: 25759527 PMCID: PMC4351209 DOI: 10.3748/wjg.v21.i9.2605] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 10/12/2014] [Accepted: 12/16/2014] [Indexed: 02/06/2023] Open
Abstract
The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. Periostin participates in normal physiological activities such as cardiac development, but is also involved in pathophysiological processes in vascular diseases, wound repair, bone formation, and tumor development. It is of increasing interest in tumor biology because it is frequently overexpressed in a variety of epithelial carcinomas and is functionally involved in multiple steps of metastasis progression. These include the maintenance of stemness, niche formation, EMT, the survival of tumor cells, and angiogenesis, all of which are indispensable for gastric cancer metastasis. Periostin has been reported to activate the PI-3K/AKT, Wnt, and FAK-mediated signaling pathways to promote metastasis. Therefore, periostin represents a potentially promising candidate for the inhibition of metastasis. In this review article, we summarize recent advances in knowledge concerning periostin, its antagonist PNDA-3, and their influence on such key processes in cancer metastasis as maintenance of stemness, niche formation, epithelial-to-mesenchymal transition, tumor cell survival, and angiogenesis. In particular, we focus our attention on the role of periostin in gastric cancer metastasis, speculate as to the usefulness of periostin as a therapeutic and diagnostic target for gastric cancer metastasis, and consider potential avenues for future research.
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Abstract
We found that the secreted protein periostin (Postn) is highly induced after partial pancreatectomy in regenerating areas containing mesenchymal stroma and tubular complexes. Importantly, after partial pancreatectomy, Postn-deficient mice exhibit impaired mesenchymal formation and reduced regeneration specifically within the pancreatic β-cell compartment. Furthermore, Postn-deficient mice demonstrate an increased sensitivity to streptozotocin. Notably, injection of Postn directly into the pancreas stimulated proliferation of vimentin-expressing cells within 24 hours, and by 3 days, a mesenchymal stroma was present containing proliferating duct-like cells expressing the progenitor markers Ngn3 and Pdx1. Intraperitoneal injection of Postn resulted in increased numbers of islets and long-term glucoregulatory benefits with no adverse effects found in other tissues. Delivery of Postn throughout the pancreas via the common bile duct resulted in increased numbers of small insulin-expressing clusters and a significant improvement in glucose tolerance. Therefore, Postn is novel molecule capable of potentiating pancreatic β-cell regeneration.
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Affiliation(s)
- Johnathan K Smid
- Sprott Center for Stem Cell Research (J.K.S., S.F., M.A.R.), Ottawa Hospital Research Institute, Regenerative Medicine Program, and University of Ottawa (J.K.S., M.A.R.), Cellular and Molecular Medicine, Faculty of Medicine, Ottawa, Ontario, Canada K1H 8L6
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Saeed AA, Sims AH, Prime SS, Paterson I, Murray PG, Lopes VR. Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan oral squamous cell carcinomas. Oral Oncol 2015; 51:237-46. [DOI: 10.1016/j.oraloncology.2014.12.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Revised: 11/26/2014] [Accepted: 12/07/2014] [Indexed: 12/13/2022]
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Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, Willbanks A, Sarkar S. EMT and tumor metastasis. Clin Transl Med 2015; 4:6. [PMID: 25852822 PMCID: PMC4385028 DOI: 10.1186/s40169-015-0048-3] [Citation(s) in RCA: 565] [Impact Index Per Article: 56.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Accepted: 01/26/2015] [Indexed: 02/07/2023] Open
Abstract
EMT and MET comprise the processes by which cells transit between epithelial and mesenchymal states, and they play integral roles in both normal development and cancer metastasis. This article reviews these processes and the molecular pathways that contribute to them. First, we compare embryogenesis and development with cancer metastasis. We then discuss the signaling pathways and the differential expression and down-regulation of receptors in both tumor cells and stromal cells, which play a role in EMT and metastasis. We further delve into the clinical implications of EMT and MET in several types of tumors, and lastly, we discuss the role of epigenetic events that regulate EMT/MET processes. We hypothesize that reversible epigenetic events regulate both EMT and MET, and thus, also regulate the development of different types of metastatic cancers.
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Affiliation(s)
- Sarah Heerboth
- />Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA USA
| | - Genevieve Housman
- />School of Human Evolution and Social Change, Arizona State University, Tempe, AZ USA
| | - Meghan Leary
- />Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA USA
| | | | - Shannon Byler
- />Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA USA
| | - Karolina Lapinska
- />Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA USA
| | - Amber Willbanks
- />Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA USA
| | - Sibaji Sarkar
- />Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA USA
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Rousseau JC, Sornay-Rendu E, Bertholon C, Chapurlat R, Garnero P. Serum periostin is associated with fracture risk in postmenopausal women: a 7-year prospective analysis of the OFELY study. J Clin Endocrinol Metab 2014; 99:2533-9. [PMID: 24628551 DOI: 10.1210/jc.2013-3893] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
PURPOSE Periostin (POSTN) is a secreted γ-carboxyglutamic acid-containing protein expressed mainly in the periosteum in adult individuals. POSNT deficient mice develop periodontis and osteoporosis with decreased bone strength. The relationship between serum POSTN and bone metabolism and fracture risk in postmenopausal women is unknown. SUBJECTS AND METHODS Serum POSTN was measured in 607 postmenopausal women (mean age 66.6 ± 8.4 y) from the Os des Femmes de Lyon cohort at the ninth annual follow-up visit (baseline visit of the current analysis). Nonvertebral and clinical vertebral incident fragility fractures were reported annually during 7 years. Areal bone mineral density (BMD; measured by dual energy X-ray absorptiometry) of the hip and bone markers (intact N-terminal propeptide of type I collagen, osteocalcin, and serum type I collagen C-telopeptide) were also measured. RESULTS At baseline, serum POSTN did not correlate with age, bone markers, and BMD. After a median of 7 years of follow-up, 75 women sustained an incident clinical vertebral or nonvertebral fragility fracture. The proportion of women who had an incident fracture was significantly higher in women with levels of POSTN in the highest quartile than that of women in the three other quartiles (19.5% vs 10.1%, P = .018) after adjustment for age and prevalent fracture. The highest quartile of POSTN was associated with an increased risk of incident fracture with a relative risk (95% confidence interval) of 1.88 (1.1-3.2) after adjustment for age, prevalent fracture, and hip BMD T-score. Patients with both low hip BMD (T-score < -2.5) and high levels of POSTN (fourth quartile) had a relative risk of fracture of 7.1 (95% confidence interval 2.4-21.8) after adjustment for age. CONCLUSION High serum POSTN levels are independently associated with increased fracture risk in postmenopausal women. These data suggest that serum POSTN could be useful to improve fracture risk assessment.
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Affiliation(s)
- J C Rousseau
- INSERM Research Unit 1033 (J.C.R., E.S.-R., C.B., R.C., P.G.), Université de Lyon, and Service de Rhumatologie et Pathologie Osseuse (R.C.), Hôpital E.-Herriot, Université de Lyon, 69437 Lyon Cedex 03, France; and Cisbio Bioassays (P.G.), 30200 Codolet, France
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Liu AY, Zheng H, Ouyang G. Periostin, a multifunctional matricellular protein in inflammatory and tumor microenvironments. Matrix Biol 2014; 37:150-6. [DOI: 10.1016/j.matbio.2014.04.007] [Citation(s) in RCA: 124] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Revised: 04/28/2014] [Accepted: 04/28/2014] [Indexed: 02/06/2023]
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Abstract
The extracellular matrix (ECM) is composed of highly variable and dynamic components that regulate cell behavior. The protein composition and physical properties of the ECM govern cell fate through biochemical and biomechanical mechanisms. This requires a carefully orchestrated and thorough regulation considering that a disturbed ECM can have serious consequences and lead to pathological conditions like cancer. In breast cancer, many ECM proteins are significantly deregulated and specific matrix components promote tumor progression and metastatic spread. Intriguingly, several ECM proteins that are associated with breast cancer development, overlap substantially with a group of ECM proteins induced during the state of tissue remodeling such as mammary gland involution. Fibrillar collagens, fibronectin, hyaluronan and matricellular proteins are matrix components that are common to both involution and cancer. Moreover, some of these proteins have in recent years been identified as important constituents of metastatic niches in breast cancer. In addition, specific ECM molecules, their receptors or enzymatic modifiers are significantly involved in resistance to therapeutic intervention. Further analysis of these ECM proteins and the downstream ECM mediated signaling pathways may provide a range of possibilities to identify druggable targets against advanced breast cancer.
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Affiliation(s)
- Thordur Oskarsson
- Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; Divison of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
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The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance. Cancer Cell Int 2014; 14:41. [PMID: 24883045 PMCID: PMC4038849 DOI: 10.1186/1475-2867-14-41] [Citation(s) in RCA: 141] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 05/09/2014] [Indexed: 12/16/2022] Open
Abstract
Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.
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Kotobuki Y, Yang L, Serada S, Tanemura A, Yang F, Nomura S, Kudo A, Izuhara K, Murota H, Fujimoto M, Katayama I, Naka T. Periostin accelerates human malignant melanoma progression by modifying the melanoma microenvironment. Pigment Cell Melanoma Res 2014; 27:630-9. [PMID: 24674392 DOI: 10.1111/pcmr.12245] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 03/24/2014] [Indexed: 11/28/2022]
Abstract
Given no reliable therapy for advanced malignant melanoma, it is important to elucidate the molecular mechanisms underlying the disease progression. Using a quantitative proteomics approach, the 'isobaric tags for relative and absolute quantitation (iTRAQ)' method, we identified that the extracellular matrix protein, periostin (POSTN), was highly expressed in invasive melanoma compared with normal skin. An immunohistochemical analysis showed that POSTN was expressed in all invasive melanoma (n = 20) and metastatic lymph node (n = 5) tissue samples, notably restricted in their stroma. In terms of the intercellular regulation of POSTN, we found that there was upregulation of POSTN when melanoma cells and normal human dermal fibroblasts (NHDFs) were cocultured, with restricted expression of TGF-β1 and TGF-β3. In a functional analyses, recombinant and NHDF-derived POSTN significantly accelerated melanoma cell proliferation via the integrin/mitogen-activated protein kinase (MAPK) signaling pathway in vitro. The size of implanted melanoma tumors was significantly suppressed in POSTN/Rag2 double knockout mice compared with Rag2 knock-out mice. These results indicate that NHDF-derived POSTN accelerates melanoma progression and might be a promising therapeutic target for malignant melanoma.
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Affiliation(s)
- Yorihisa Kotobuki
- Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan; Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan
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Conway SJ, Izuhara K, Kudo Y, Litvin J, Markwald R, Ouyang G, Arron JR, Holweg CTJ, Kudo A. The role of periostin in tissue remodeling across health and disease. Cell Mol Life Sci 2014; 71:1279-88. [PMID: 24146092 PMCID: PMC3949008 DOI: 10.1007/s00018-013-1494-y] [Citation(s) in RCA: 275] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 10/04/2013] [Accepted: 10/07/2013] [Indexed: 12/22/2022]
Abstract
Periostin, also termed osteoblast-specific factor 2, is a matricellular protein with known functions in osteology, tissue repair, oncology, cardiovascular and respiratory systems, and in various inflammatory settings. However, most of the research to date has been conducted in divergent and circumscribed areas meaning that the overall understanding of this intriguing molecule remains fragmented. Here, we integrate the available evidence on periostin expression, its normal role in development, and whether it plays a similar function during pathologic repair, regeneration, and disease in order to bring together the different research fields in which periostin investigations are ongoing. In spite of the seemingly disparate roles of periostin in health and disease, tissue remodeling as a response to insult/injury is emerging as a common functional denominator of this matricellular molecule. Periostin is transiently upregulated during cell fate changes, either physiologic or pathologic. Combining observations from various conditions, a common pattern of events can be suggested, including periostin localization during development, insult and injury, epithelial-mesenchymal transition, extracellular matrix restructuring, and remodeling. We propose mesenchymal remodeling as an overarching role for the matricellular protein periostin, across physiology and disease. Periostin may be seen as an important structural mediator, balancing appropriate versus inappropriate tissue adaption in response to insult/injury.
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Affiliation(s)
- Simon J. Conway
- Program in Developmental Biology and Neonatal Medicine, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN USA
| | - Kenji Izuhara
- Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan
| | - Yasusei Kudo
- Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
| | - Judith Litvin
- Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA USA
| | - Roger Markwald
- Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC USA
| | - Gaoliang Ouyang
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China
| | | | | | - Akira Kudo
- Department of Biological Information, Tokyo Institute of Technology, 4259 B-33, Nagatsuta, Midori-ku, Yokohama 226-8501 Japan
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Zhu J, Xiong G, Trinkle C, Xu R. Integrated extracellular matrix signaling in mammary gland development and breast cancer progression. Histol Histopathol 2014; 29:1083-92. [PMID: 24682974 DOI: 10.14670/hh-29.1083] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.
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Affiliation(s)
- Jieqing Zhu
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - Gaofeng Xiong
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | | | - Ren Xu
- Markey Cancer Center, and Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA.
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Nuzzo PV, Buzzatti G, Ricci F, Rubagotti A, Argellati F, Zinoli L, Boccardo F. Periostin: a novel prognostic and therapeutic target for genitourinary cancer? Clin Genitourin Cancer 2014; 12:301-11. [PMID: 24656869 DOI: 10.1016/j.clgc.2014.02.005] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 01/29/2014] [Accepted: 02/12/2014] [Indexed: 01/21/2023]
Abstract
Many of the cellular abnormalities present in solid tumors are structural in nature and involve the proteins of the extracellular matrix (ECM). Periostin is a protein produced and secreted by the fibroblasts as a component of the ECM where it is involved in regulating intercellular adhesion. The expression of periostin has an important physiological role during embryogenesis and growth, namely at the level of bone, dental, and cardiac tissues. Many studies indicate that periostin plays an important role for tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. To the best of our knowledge, a limited number of studies have investigated periostin expression in urogenital cancer, such as prostate, bladder, penile, and renal cancer, and no studies were performed in testis cancer. In this review article, we summarize the most recent knowledge of periostin, its genetic and protein structure, and the role of the different isoforms identified and sequenced so far. In particular, we focus our attention on the role of this protein in genitourinary tumors, trying to emphasize the role not only as a possible prognostic marker, but also as a possible target for the development of future anticancer therapies.
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Affiliation(s)
- Pier Vitale Nuzzo
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; Department of Internal Medicine, University of Genoa, School of Medicine, Genoa, Italy
| | - Giulia Buzzatti
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; Department of Internal Medicine, University of Genoa, School of Medicine, Genoa, Italy
| | - Francesco Ricci
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; IRCCS San Martino University Hospital - IST National Cancer Research Institute, Genoa, Italy
| | - Alessandra Rubagotti
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; Department of Internal Medicine, University of Genoa, School of Medicine, Genoa, Italy; IRCCS San Martino University Hospital - IST National Cancer Research Institute, Genoa, Italy
| | - Francesca Argellati
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; IRCCS San Martino University Hospital - IST National Cancer Research Institute, Genoa, Italy
| | - Linda Zinoli
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; Department of Internal Medicine, University of Genoa, School of Medicine, Genoa, Italy; IRCCS San Martino University Hospital - IST National Cancer Research Institute, Genoa, Italy
| | - Francesco Boccardo
- Academic Unit of Medical Oncology (Medical Oncology B), University of Genoa, School of Medicine, Genoa, Italy; Department of Internal Medicine, University of Genoa, School of Medicine, Genoa, Italy; IRCCS San Martino University Hospital - IST National Cancer Research Institute, Genoa, Italy.
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